Two studies, one published in February and one in March, bring into clearer
focus the gene implicated in Alzheimer's disease. One study shows the
limitations of genetic testing; the other suggests that the genetic factor
affects races differently.

In one study, apolipoprotein-E (APOE) genotyping for
Alzheimer's was shown to be of significant value in diagnosing the disease only
when coupled with old-fashioned medicine-a thorough clinical evaluation.

The
study, reported in the Feb. 18, 1998, issue of the New England Journal of
Medicine, emphasizes that results from testing for the presence of the e4 form
of APOE by itself is inconclusive and does not provide sufficient evidence to
diagnose Alzheimer's disease. Researchers discovered that when the APOE test is
administered along with a thorough examination, the validation of the clinical
diagnosis of Alzheimer's disease could be greatly improved. The study is the
largest cooperative investigation to date involving 26 federally funded
Alzheimer's disease centers nationwide, including P&S researchers in
collaboration with the National Institute on Aging.

"The apolipoprotein E
genotype may be undeniable as a genetic risk factor for Alzheimer's disease, but
its use as a diagnostic aid has received little attention until now," says Dr.
Richard Mayeux, senior author and Gertrude H. Sergievsky Professor of Neurology,
Psychiatry, and Public Health (epidemiology), and co-director of the Taub Center
for Alzheimer's Disease Research.

Investigators, led by Dr. Mayeux, reviewed the
eligibility of men and women referred to the 26 Alzheimer's disease centers for
diagnosis of dementia. The study examined records of 1,108 women and 1,080 men.
Each patient examined had a battery of clinical and behavioral tests, followed
by numerous laboratory and brain imaging studies. The patients were followed
throughout the course of their disease and their brains were examined after they
died.

Based on autopsies, Dr. Mayeux found that 93 percent of the patients who
were found to have Alzheimer's had been diagnosed by a physician as having the
disease. However, 45 percent of individuals found to have other forms of
dementia at the time of autopsy also had been diagnosed by physicians as having
Alzheimer's. This high rate of false positive diagnoses shows the limitations of
using recommended clinical criteria alone. But by testing for the APOE genotype
only in patients who first met clinical criteria for Alzheimer's, the false
positive diagnoses decreased from 45 percent to 16 percent.

Dr. Mayeux cautions
that the study was done in a selected group of people who received treatment in
specialized centers for Alzheimer's disease so the results may not apply to all
individuals. "More broad-based study is needed before these results can be
assumed to be universally applicable."

The study's other P&S authors were Dr.
Steven Shea and Dr. Ming-Xin Tang.

The other study, reported in the March 11,
1998, issue of the Journal of the American Medical Association, examined the
effect of the presence of APOE-e4 on increased risk of Alzheimer's disease among
African-Americans and Hispanics. The study found that African-Americans and
Hispanics have an increased risk of Alzheimer's disease whether or not they
carry APOE-e4.

African-Americans and Hispanics with APOE-e4 have approximately
the same risk of Alzheimer's disease as do whites with the allele, the study
found. But African-Americans without the APOE-e4 genotype have four times the
risk of developing Alzheimer's disease than do whites without the genotype, and
Hispanics have 2.5 times the risk.

The study's lead author, Dr. Ming-Xin Tang,
and colleagues determined the genotypes of approximately 1,000 elderly
volunteers, all residents of Washington Heights. The researchers then monitored
the health of the volunteers over five years to assess them for signs of
Alzheimer's disease (all volunteers were free of any signs of disease at the
start of the study). The researchers controlled for other factors that might
affect risk for the disease, such as education levels. And to reduce the
likelihood that the results might be swayed by a misdiagnosis of Alzheimer's,
the researchers also calculated their results only among those who developed
severe forms of the disease.

The researchers are not certain what causes the
increased risk among the two minority groups. "It could be genetic or it could
be due to environmental factors," says Dr. Tang, assistant professor of public
health (biostatistics) in the Sergievsky Center. Researchers are planning a
follow-up study.

Dr. Mayeux notes, "This research highlights an important point:
When something is found to be true among whites, we can't automatically assume
it will be true for other ethnic groups as well."